Disorder Related to Renal Transplantation, Hypercholesterolemia
Conditions
Keywords
Immunosuppression, Everolimus, rosuvastatin, fluvastatin, Lipid lowering
Brief summary
Renal transplant recipients need life long immunosuppression and one of the new drugs is everolimus. Everolimus is a potent immunosuppressive drug and one of the main side-effects are increased blood cholesterol levels. Many renal transplant recipients are treated with a cholesterol lowering agent, mainly fluvastatin. Rosuvastatin is a new cholesterol lowering drug on the market with a potential higher cholesterol lowering potency. In the present study the investigators will examine the hypothesis that rosuvastatin reduce cholesterol levels more than fluvastatin in renal transplant patients.
Interventions
DRUGRosuvastatin
20 mg rosuvastatin for 4 weeks
Sponsors
Oslo University Hospital
University of Oslo School of Pharmacy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Renal transplant recipients with stable renal function (plasma creatinine \< 200 µmol/L) * Renal transplant recipients on an everolimus and fluvastatin based therapy for minimum 3 months prior to inclusion * \> 18 years of age * Male patient or female patient without childbearing potential (surgically sterilized or postmenopausal) or if female of childbearing potential; is not lactating, has a negative pregnancy test at screening and is willing to utilize an effective method of contraception throughout the study period and for 90 days following discontinuation of the study drugs * Signed informed consent
Exclusion criteria
* Patients experiencing an acute rejection episode within 2 weeks before or after inclusion, whether proven by biopsy or not * Patients with a known hypersensitivity to rosuvastatin * Change in enzyme inducing or inhibiting drugs within the last 2 weeks prior to and throughout the study \[e.g. barbiturates, rifampicin, ketoconazole, erythromycin, cimetidine and similar drugs\] * Pregnant or nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| compare the treatment efficacy (blood lipid lowering effect) of rosuvastatin versus fluvastatin | 4 weeks | Compare the blood lipid levels before and after switch from fluvastatin to rosuvastatin |
| Area Under Curve (AUC) of rosuvastatin in renal transplant recipients treated with everolimus. Time frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post dose. | 4 weeks | Compare 24-h pharmacokinetics of renal transplant recipients with historic controls |
Secondary
| Measure | Time frame |
|---|---|
| 2. Investigate P-gp activity in whole blood in everolimus treated patients | 4 weeks |
| 4. Compare effect of rosuvastatin versus fluvastatin therapy on the renal function (eGFR) | 4 weeks |
| 3. Study inter individual variation in rosuvastatin and everolimus pharmacokinetics in renal transplant recipients due to polymorphism in the genes encoding P-gp, OATP1B1 and CYP3A5 | 4 weeks |
| 1. Area Under Curve (AUC) of everolimus during rosuvastatin versus fluvastatin therapy, including intracellular everolimus concentrations within T-lymphocytes. Time frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours post-dose. | 4 weeks |
Countries
Norway
Outcome results
None listed